Spontaneous Gene Mutations in Autistic Children: What Causes ASDs?
A week ago, a new study published in the Archives of General Psychiatry found that the autism rate in a community in South Korea is 2.6% or 1 in 38, a far higher estimate than ever before accounted for. Just a generation ago, autism was considered a rare disorder, found in perhaps in 1 in 10,000 children, so it’s no wonder that people are asking “why.” Many point to the past decade’s expanded diagnostic criteria for autism as a likely reason for the increase in the prevalence rate of autism to the point that some talk about an epidemic.
In the absence of any definite explanations, theories about vaccines or something in vaccines or highway pollution or when a child is conceived or all manner of environmental agents persist. Scientists also continue to research the genetics of autism, though the genes they’ve identified tend to be found in only a few individuals.
A new study published in Nature Genetics will not stop the proliferation of this or that causing autism. But consideration of its findings offers families some helpful clues, as well as suggesting that sometimes a child becomes autistic because such things happen in nature.
The Howard Hughes Medical Institute describes how researchers using “high-throughput gene sequencing technology” were able to identify several de novo or spontaneous gene mutations in 20 children with sporadic autism spectrum disorders — that is, their family members showed no other sign of autism.
More details, with some emphases by me in boldface to highlight traits that are seen in autistic individuals:
The team identified 21 spontaneous mutations — meaning they weren’t inherited from either parent — in the children’s DNA. Eleven of these were mutations that would alter the protein encoded by the affected gene. In four of the 20 children, the researchers found mutations that were severe, some of which have been previously linked to autism, intellectual disability, and epilepsy.
For example, one child had a mutation in the GRIN2B gene, which is crucial for neuronal signaling. Mutations in the gene had already been seen in people with intellectual disability and epilepsy, suggesting that mutations in the same gene can manifest in a variety of ways.
Another individual had an extra nucleotide in FOXP1, a gene that, along with its close relatives, has been heavily implicated in language defects. In the same child, an additional gene mutation that was inherited occurred within the same pathway, giving way to a genetic “double jeopardy,” says [Evan E. Eichler at the University of Washington School of Medicine]. “It’s probably not a coincidence that if we look at this family specifically, this child has the most severe speech delay of all the kids we’ve looked at,” he adds.
These new findings support the ‘multi-hit’ model of autism, which suggests that having more than one mutation can cause or worsen symptoms of autism and other brain disorders. The different combinations of mutations may contribute to the heterogeneity in ASDs. “The idea that multiple genes are coming together in what’s called the oligogenic model of autism is, I think, an exciting but also daunting prospect,” Eichler says.
That such different combinations of genetic mutations contribute to a child being autistic could account for why individuals with an ASD diagnosis have some very similar, and very different, features.
On a personal note, my husband Jim Fisher and I have been curious about genetic studies. While there’s no one in either of our families who has an autism diagnosis or who is exactly like him, we see plenty of ourselves and our different “neurological wiring” in Charlie: Between us and our families, there’s ADHD, bipolar disorder, OCD, anxiety and possibly Asperger’s Syndrome (though not at all diagnosed).
On the one hand, genetic studies like the one described above suggest how “de novo” Charlie became Charlie. But genetic studies can also confirm how Charlie is not some changeling child we’re “stuck” with, but — to refer to the title of a friend’s memoir about his autistic son — very much one of us.
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